Studies of aerobic metabolism in Giardia lamblia have disclosed a novel enzyme system which catalyzes the oxidation of pyruvate in the presence of coenzyme A, and couples the oxidation to the synthesis of ATP. Calmodulin, isolated from disrupted trophozoites of axenized G. lamblia has been purified by hydrophobic and ion exchange chromatography to apparent homogenity (MW=20,000). The protozoan calmodulin also has been purified in large quantities by Fast Protein Liquid Chromatography and shown to retain its biological activity (activation of phosphodiesterase). Partial characterization of the purified protein has been accomplished. In an attempt to assess the physiological role of calmodulin in G. lamblia; a study of calcium transport was initiated. Intact trophozoites rapidly accumulate Ca2+ in the presence of glucose and Pi. The uptake is inhibited by known inhibitors of calmodulin, indicative of its regulatory role in the transport of this vital cation. Continued studies of mammalian mitochondria have shown that the tricyclic antidepressant drugs imipramine and chlorimipramine have multiple, adverse effects on energy metabolism. The latter drug also has cidal actions on the enteric protozoa, and on Leishmania donovani. Initial studies of energy metabolism in human platelets showed that the tricyclic drugs also inhibit the respiratory burst elicited by thrombin. Further studies are planned to evaluate the physiological significance of these interesting findings. Apart from the intrinsic interest of investigating a process vital to all living cells, this project has demonstrated how fundamental studies in one area (mammalian bioenergetics) can lead to unexpected, and possibly, applied results in another (parasite metabolism, and cidal action of antidepressant drugs).